PB1815: T(8;16)(P11;P13): A RARE CASE OF ACUTE MYELOID LEUKEMIA
Authors: R. Cuccurullo, G. Aloj, A. De Matteo, G. Giagnuolo, F. Cacace, M. L. Conelli, L. Bufalo, F. P. Tambaro, G. Menna
Journal: HemaSphere (2022)

Background: Acute myeloid leukemia (AML) with t(8;16) is a rare AML subtype (0.2% in adult setting) that represents a distinct clinical entity, often therapy-related. t(8;16)(p11;p13) involves MYST histone acetyltransferarse 3 (MYST3) gene on chromosome 8p11 and cAMP response element binding protein (CREBBP) gene on chromosome 16p13. Both genes code for proteins with histone acetyltransferase activity crucial for cell cycle control. Pediatric t(8;16) AML may be associated with extramedullary disease, high rate of Disseminated Intravascular Coagulation (DIC), FAB M4 or M5 morphology. In neonatal cases spontaneus regression is frequently observed. Aims: To report on a pediatric case of the rare AML with t(8;16)(p11;p13). Methods: A 12 year-old female was hospitalized for hypermenorrhea, drop attack, fatigue and leukocytosis. Clinical examination showed: paleness, diffuse pain, petechiae to the oral mucosa. No organomegaly was detected. At peripheral blood cells count she had serum hemoglobin of 5 g/dL, 78.900/mm3 White Blood Cells (WBC) and 96.000/mm3 platelets. Fibrinogen was diminished (32 mg/dL; range 150-400 mg/dL) while D-Dimers were elevated (30.644 ng/ml; Range 0-500) as laboratory signs of DIC. Peripheral blood smear showed myeloid blasts. Platelets and plasma transfusions were performed. Myeloid blast combined to DIC suggested acute promyelocitic leukemia presumptive diagnosis but t(15;17) was not found at PCR rapid test. Bone marrow observation confirmed AML-M5 diagnosis with monocytoid blasts infiltrate. Central Nervous System involvement was ruled out by lumbar puncture. The patient was enrolled in AIEOP LAM 2013-01 protocol. Before first chemotherapy administration, spontaneous WBC reduction was observed (6.730/mm3). The hemorrhagic diathesis worsened drammatically during the second day of chemotherapy with bleeding from the central venous catheter insertion site. The blood tests revealed rapid decrease of WBC to 1.240/mm3, platelet and fibrinogen respectively to 34.000/mm3 and 57 mg/dL, while D-Dimers raised to 113.304 ng/ml and INR became 2.04. During the following days of chemotherapy, the performance status of the patient improved and the bleeding episodes decreased. WBC count progressively declined while platelet count and fibrinogen level gradually raised to better values; D-Dimers level and INR progressively recovered too. Bone marrow molecular biology revealed the presence of t(8;16)(p11;p13). In addition, a complex karyotipe (45XX,t(8;16)(p11;p13),-9[4]/46XX,t(8;16)(p11;p13),-9,+21[1]/46XX[1]) was found during the cytogenetic tests. According to protocol LAM 2013-01, both these features are predictive of poor prognosis, therefore the patient was enrolled in the high risk therapeutic outline, receiving four cycles of chemotherapy (ICE, ICE, AVE, HAM) and bone marrow transplantation. She achieved hematological complete remission after the first cycle of chemotherapy, maintaining that until an HLA identical sibling bone marrow transplant was performed. Results: Actually, 7 months after the trasplant, the patient is in complete remission. Summary/Conclusion: t(8;16) AML is a rare pediatric leukemia, characterized by M4/M5 morphology, high frequency of extramedullar involvement, complex karyotipe and DIC. Spontaneous remission often occur in neonatal cases. In our case, the presence of t(8;16) could explain the WBC reduction before the administration of chemotherapy. The knowledge of this entity is importat to quickly recognize the correct diagnosis and to begin the proper therapy as soon as possible, avoiding major complications due to coagulopathy.